Nitric oxide, which is a radical molecule having high reactivity, is a gas synthesized by nitric oxide synthase in cells and has an important function as a bioactive compound in the body. Particularly, nitric oxide has been known to be associated with various physiological phenomena such as a neurotransmission system, a cardiovascular system, an immune system, and the like, and diseases.
For example, nitric oxide has contrary therapeutic effects in accordance with a concentration and a release time thereof. It has been known that when high-concentration nitric oxide is released for a short time, an anti-cancer effect and anti-bacterial effect are exhibited, and when a small amount of nitric oxide is released for a long period of time, nitric oxide is associated with wound treatment, cell growth, angiogenesis, and the like. However, since nitric oxide exists in a gas form, there is a large limitation in effectively delivering nitric oxide.
Diazeniumdiolate, which is a representative functional group releasing nitric oxide, is also referred to as NONOate, and may be represented by General Formula, RR′N—N(O)═NOR″. Diazeniumdiolate may be stably stored in a solid form, has high solubility in water, and is decomposed under the body temperature and pH conditions, and a release form thereof is variously changed depending on pH. Diazeniumdiolate may easily produce nitric oxide and release a relatively large amount of nitric oxide, but there is a problem in that diazeniumdiolate releases nitric oxide while simultaneously contacting water.
In order to overcome this problem, a technology of releasing nitric oxide by external stimuli has been developed, but a case in which both the external stimuli and biocompatible product are applied is significantly rare. The present applicant tried to introduce a novel system of inducing release of nitric oxide by a change in pH while blocking a contact with the outside by introducing calcium phosphate, which is a biocompatible material. Further, the present applicant tried to develop a system of more stably delivering nitric oxide while minimizing a loss of nitric oxide generated in a delivery process.